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Veteriner Tıbbî Ürünlerde Safsızlıklar

Year 2020, Volume: 31 Issue: 2, 201 - 210, 31.12.2020
https://doi.org/10.35864/evmd.753362

Abstract

Tıbbi Ürünlerin içermiş oldukları arzu edilmeyen bileşenlerin belirlenmesi, farmasötik kalitenin teminatı açısından bir ön koşuldur. Tıbbi ürünlerde etkin madde ve yardımcı maddeler dışında kalan herhangi bir bileşen olan safsızlıkların kontrolü ise bu güvencenin en kritik ve kompleks parametrelerinden birisidir. Farklı başlangıç materyalleri kullanılarak farklı formülasyonlarla geliştirilen ürünlerde bu parametrenin çeşitliliği, kontrolünün zorluğunu ve beraberinde getirdiği riskleri daha da artmaktadır. Binlerce bebeğin deformitelere sahip olarak doğmasına neden olan talidomid’in (R)-izomerinin terapötik etkinliğe, (S)-izomerinin teratojenik etkiye sahip olduğu anlaşılarak, tıbbi ürün güvenilirliğinde bir milat olarak tüm düzenlemelerin yeniden şekillenmesine neden olmuştur. Veteriner tıbbi ürünlerin kapsamı tür çeşitliliği, hedef hayvan güvenliği, tüketici güvenliği, gıda güvenliği, kullanıcı güvenliği, çevresel güvenilirlik ve antimikrobiyel direnç yönleriyle beşeri tıbbi ürünlere göre daha geniştir. İlaç ürününün her hangi bir dozaj biriminin aynı miktarda aktif bileşen vermesi ve mümkün olduğunca safsızlık içermemesi amacıyla kalite kontrol uygulamaları kapsamında gerçekleştirilen safsızlık kontrolleri ve bu konudaki mevzuatlar oldukça komplekstir. İlaç üreticisinden tüketicisine kadar geniş bir kitleyi ilgilendiren safsızlık konusunun ele alındığı bu derlemede; dünyada önemi günden güne artan veteriner tıbbi ürün organik ve DNA reaktif safsızlıklara ilişkin güncel mevzuat ile bu safsızlıkların önlenmesine yönelik rasyonel öneriler sunulmaya çalışılmıştır.

Supporting Institution

Tarım ve Orman Bakanlığı Tarımsal Araştırmalar ve Politikalar Genel Müdürlüğü-TAGEM

Project Number

20

References

  • American Chemical Society, (ACS), (2014). https://www.acs.org/content/acs/en/molecule-of-the-week/archive/t/thalidomide.html. Erişim Tarihi: 04.12.2019
  • Anonim, (2009). European Commision, Regulation (EC) No 470/2009. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32009R0470 Erişim Tarihi; 27.03.2020.
  • Anonim, (2011). Veteriner Tıbbi Ürünler Hakkında Yönetmelik. Resmi Gazete, 24.12.2011-28152. Erişim Tarihi:20.01.2020.
  • Anonim, (2012). İmmünolojik Veteriner Tıbbi Ürünler Dışındaki Veteriner Tıbbi Ürünlerin Başvuru Dosyası Kılavuzu. Erişim Tarihi: 20.01.2020, https://kms.kaysis.gov.tr/(X(1)S(13uw3bibpicsqth4um00cotp))/Home/Goster/56460?AspxAutoDetectCookieSupport=1.
  • Anonim, (2012a). Veteriner Tıbbi Ürünler İçin İyi Üretim Uygulamaları (GMP) Kılavuzu, https://www.tarimorman.gov.tr/GKGM/Belgeler/Veteriner%20Hizmetleri/vetsagurun/VTU_icin_GMP_Klavuzu.pdf Erişim Tarihi:14.03.2020.
  • Anonim, (2015). European Commission. The Rules Governing Medicinal Products in the European Union: Volume 6B Notice to applicants, Veterinary Medicinal Products, Presentation and Content of the Dossier.
  • Bakırel T, (2020). Hayvansal Gıdalarda İlaç Kalıntıları ve Veteriner Tıbbi Ürünlerin Ruhsatlandırılması. Atatürk Üniversitesi Açıköğretim Fakültesi Yayını, 198-225.
  • Devlet Planlama Teşkilatı (DPT), (2007). Dokuzuncu kalkınma planı (2007-2013): İlaç Sanayi Özel İhtisas Komisyonu Raporu.
  • Elder D P, Kuentz M, Holm R, (2016). Pharmaceutical excipients—quality, regulatory and biopharmaceutical considerations. European Journal of Pharmaceutical Sciences, 87, 88-99. DOI: 10.1016/j.ejps.2015.12.018
  • Erkeoğlu P, Baydar T, Şahin G, (2014). Toksikolojik Açıdan İlaç Safsızlıkları. Turkiye Klinikleri J Pharm Sci 2014;3(2). doi: 10.5336/pharmsci.2014-41382
  • European Medicines Agency (EMA), (1991). Guideline: Specifications and Control Tests on the Finished Product.
  • European Medicines Agency (EMA), (1993). Investigation of Chiral Active Substances.
  • European Medicines Agency, (EMA), (2007). Opinion, https://www.ema.europa.eu/en/documents/other/chmp-scientific-article-53-opinion-potential-risks-carcinogens-mutagens-substances-toxic_en.pdf Erişim Tarihi; 27.06.2019.
  • European Medicine Agency (EMA) (2007a). Recommendation On The Evaluation Of The Benefit-Risk Balance Of Veterinary Medicinal Products.
  • European Medicine Agency (EMA) (2007b). Guideline on Stability Testing: Stability Testing of New Drug Substances and Medicinal Products. EMEA/CVMP/VICH/899/99-Rev.1.
  • European Medicine Agency (EMA) (2008). Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished Products. EMEA/CVMP/QWP/846/99-Rev.1.
  • European Medicines Agency (EMA), (2009). Recommendation on the assessment of the quality of medicinal products containing existing/known active substances.
  • European Medicines Agency (EMA), (2015). Guideline on the assessment of persistent, bioaccumulative and toxic PBT) or very persistent and very bioaccumulative (vPvB) substances in veterinary medicinal products.
  • European Medicines Agency (EMA), (2017). Implementation of risk assessment requirements to control elemental impurities in veterinary medicinal products. EMA/CVMP/QWP/631010/2017.
  • European Medicines Agency (EMA), (2018). CVMP assessment report regarding the request for an opinion under Article 30(3) of Regulation (EC) No. 726/2004 For veterinary medicinal products containing gentamicin for parenteral administration to horses.
  • European Medicines Agency (EMA), (2018a). Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products. EMA/CVMP/SWP/377245/2016.
  • Flamand N, Meunier JR, Meunier PA, Agapakis-Causse C, (2001). Mini mutagenicity test: a miniaturized version of the Ames test used in a prescreening assay for point mutagenesis assessment. Toxicology in vitro, 15(2), 105-114.
  • Food and Drug Administration (FDA), (2020). Inactive Ingredient Database. https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm Erişim Tarihi; 08.03.2020.
  • International Conference on Harmonisation (ICH), (1990). History. https://www.ich.org/about/history.html, Erişim Tarihi:11.11.2019.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (1993). https://vichsec.org/, Erişim Tarihi:11.11.2019.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2005). GL39 (Quality), Test procedures and acceptance criteria for new veterinary drug substances and new medicinal products: chemical substances.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2007). VICH GL10 (Quality), Impurities In New Veterinary Drug Substances.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products, (VICH), (2007a). VICH GL11 (Quality), Impurities In New Veterinary Medicinal Products.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2011). VICH GL18 (Quality), Impurities: Residual Solvents In New Veterinary Medicinal Products, Active Substances And Excipients.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2014). VICH GL23 (Safety), Studies To Evaluate The Safety Of Residues Of Veterinary Drugs In Human Food: Genotoxicity Testing.
  • Jacobson-Kram D, McGovern T, (2007). Toxicological overview of impurities in pharmaceutical products. Advanced drug delivery reviews, 59(1), 38-42. DOI: 10.1016/j.addr.2006.10.007
  • Liu KT, Chen CH, (2019). Determination of Impurities in Pharmaceuticals: Why and How?. In Quality Management and Quality Control-New Trends and Developments. IntechOpen. DOI: 10.5772/intechopen.83849
  • Mike F, Pehlivan SB, Öner L, (2014). Farmasötik Ürünlerde Tasarımla Kalite Yaklaşımı. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (2), 203-230.
  • Organisation for Economic Co-operation and Development (OECD), (2015). Guidance Document on Revisions to OECD Genetic Toxicology Test Guidelines.
  • Akı-Yalçın E, (2017). Kantitatif Yapı-Etki İlişkileri Analizinde Kullanılan Fizikokimyasal Parametreler (QSAR Parametreleri). Sunu. Ankara Üniversitesi. http://www.esisresearch.org/Uploads/Documents/qsar_parametreler_2017.pdf Erişim Tarihi; 03.05.2020.
  • Pilaniya K, Chandrawanshi HK, Pilaniya U, Manchandani P, Jain P, Singh B, (2010). Recent trends in the impurity profile of pharmaceuticals. J Adv Pharm Technol Res, 2010 Jul-Sep; 1(3): 302–310. DOI: 10.4103/0110-5558.72422
  • Pindelska E, Sokal A, Kolodziejski W, (2017). Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques. Advanced drug delivery reviews, 111-146. https://doi.org/10.1016/j.addr.2017.09.014
  • Plošnik A, Vračko M, Sollner Dolenc M, (2016). Mutagenic and carcinogenic structural alerts and their mechanisms of action. Arhiv za higijenu rada i toksikologiju, 67(3), 169-182. DOI: 10.1515/aiht-2016-67-2801
  • Rägo L, Santoso B, (2008). Drug Regulation: History, Present and Future, WHO, 65-76.
  • Smith S, (2009). Chiral Toxicology: It’s the Same Thing...Only Different, Toxicological Sciences, 110(1), 4–30. DOI: 10.1093/toxsci/kfp097
  • Tian Y, Chang Y, Feng YC, Zhang DS, Hu C, (2015). Isolation, identification and characterization of related substances in furbenicillin. The Journal of Antibiotics, 68(2), 133-136. DOI: 10.1038/ja.2014.145
  • Vargesson N, (2015). Thalidomide‐induced teratogenesis: History and mechanisms, Birth Defects Res C Embryo Today, Jun; 105(2): 140–156. DOI: 10.1002/bdrc.21096
  • Wu Y, Levons J, Narang AS, Raghavan K, Rao VM, (2011). Reactive impurities in excipients: profiling, identification and mitigation of drug–excipient incompatibility. AAPS PharmSciTech, 12(4), 1248-1263. DOI: 10.1208/s12249-011-9677-z
  • Ziegelbauer HE, Aubrecht J, Kleinjans JC, Ahr HJ, (2009). “Applications of toxicogenomics to study mechanisms of genotoxicity and carcinogenicity”. Toxicol Lett. 2009, 186, 36-44. DOI: 10.1016/j.toxlet.2008.08.017
Year 2020, Volume: 31 Issue: 2, 201 - 210, 31.12.2020
https://doi.org/10.35864/evmd.753362

Abstract

Project Number

20

References

  • American Chemical Society, (ACS), (2014). https://www.acs.org/content/acs/en/molecule-of-the-week/archive/t/thalidomide.html. Erişim Tarihi: 04.12.2019
  • Anonim, (2009). European Commision, Regulation (EC) No 470/2009. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32009R0470 Erişim Tarihi; 27.03.2020.
  • Anonim, (2011). Veteriner Tıbbi Ürünler Hakkında Yönetmelik. Resmi Gazete, 24.12.2011-28152. Erişim Tarihi:20.01.2020.
  • Anonim, (2012). İmmünolojik Veteriner Tıbbi Ürünler Dışındaki Veteriner Tıbbi Ürünlerin Başvuru Dosyası Kılavuzu. Erişim Tarihi: 20.01.2020, https://kms.kaysis.gov.tr/(X(1)S(13uw3bibpicsqth4um00cotp))/Home/Goster/56460?AspxAutoDetectCookieSupport=1.
  • Anonim, (2012a). Veteriner Tıbbi Ürünler İçin İyi Üretim Uygulamaları (GMP) Kılavuzu, https://www.tarimorman.gov.tr/GKGM/Belgeler/Veteriner%20Hizmetleri/vetsagurun/VTU_icin_GMP_Klavuzu.pdf Erişim Tarihi:14.03.2020.
  • Anonim, (2015). European Commission. The Rules Governing Medicinal Products in the European Union: Volume 6B Notice to applicants, Veterinary Medicinal Products, Presentation and Content of the Dossier.
  • Bakırel T, (2020). Hayvansal Gıdalarda İlaç Kalıntıları ve Veteriner Tıbbi Ürünlerin Ruhsatlandırılması. Atatürk Üniversitesi Açıköğretim Fakültesi Yayını, 198-225.
  • Devlet Planlama Teşkilatı (DPT), (2007). Dokuzuncu kalkınma planı (2007-2013): İlaç Sanayi Özel İhtisas Komisyonu Raporu.
  • Elder D P, Kuentz M, Holm R, (2016). Pharmaceutical excipients—quality, regulatory and biopharmaceutical considerations. European Journal of Pharmaceutical Sciences, 87, 88-99. DOI: 10.1016/j.ejps.2015.12.018
  • Erkeoğlu P, Baydar T, Şahin G, (2014). Toksikolojik Açıdan İlaç Safsızlıkları. Turkiye Klinikleri J Pharm Sci 2014;3(2). doi: 10.5336/pharmsci.2014-41382
  • European Medicines Agency (EMA), (1991). Guideline: Specifications and Control Tests on the Finished Product.
  • European Medicines Agency (EMA), (1993). Investigation of Chiral Active Substances.
  • European Medicines Agency, (EMA), (2007). Opinion, https://www.ema.europa.eu/en/documents/other/chmp-scientific-article-53-opinion-potential-risks-carcinogens-mutagens-substances-toxic_en.pdf Erişim Tarihi; 27.06.2019.
  • European Medicine Agency (EMA) (2007a). Recommendation On The Evaluation Of The Benefit-Risk Balance Of Veterinary Medicinal Products.
  • European Medicine Agency (EMA) (2007b). Guideline on Stability Testing: Stability Testing of New Drug Substances and Medicinal Products. EMEA/CVMP/VICH/899/99-Rev.1.
  • European Medicine Agency (EMA) (2008). Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished Products. EMEA/CVMP/QWP/846/99-Rev.1.
  • European Medicines Agency (EMA), (2009). Recommendation on the assessment of the quality of medicinal products containing existing/known active substances.
  • European Medicines Agency (EMA), (2015). Guideline on the assessment of persistent, bioaccumulative and toxic PBT) or very persistent and very bioaccumulative (vPvB) substances in veterinary medicinal products.
  • European Medicines Agency (EMA), (2017). Implementation of risk assessment requirements to control elemental impurities in veterinary medicinal products. EMA/CVMP/QWP/631010/2017.
  • European Medicines Agency (EMA), (2018). CVMP assessment report regarding the request for an opinion under Article 30(3) of Regulation (EC) No. 726/2004 For veterinary medicinal products containing gentamicin for parenteral administration to horses.
  • European Medicines Agency (EMA), (2018a). Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products. EMA/CVMP/SWP/377245/2016.
  • Flamand N, Meunier JR, Meunier PA, Agapakis-Causse C, (2001). Mini mutagenicity test: a miniaturized version of the Ames test used in a prescreening assay for point mutagenesis assessment. Toxicology in vitro, 15(2), 105-114.
  • Food and Drug Administration (FDA), (2020). Inactive Ingredient Database. https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm Erişim Tarihi; 08.03.2020.
  • International Conference on Harmonisation (ICH), (1990). History. https://www.ich.org/about/history.html, Erişim Tarihi:11.11.2019.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (1993). https://vichsec.org/, Erişim Tarihi:11.11.2019.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2005). GL39 (Quality), Test procedures and acceptance criteria for new veterinary drug substances and new medicinal products: chemical substances.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2007). VICH GL10 (Quality), Impurities In New Veterinary Drug Substances.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products, (VICH), (2007a). VICH GL11 (Quality), Impurities In New Veterinary Medicinal Products.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2011). VICH GL18 (Quality), Impurities: Residual Solvents In New Veterinary Medicinal Products, Active Substances And Excipients.
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), (2014). VICH GL23 (Safety), Studies To Evaluate The Safety Of Residues Of Veterinary Drugs In Human Food: Genotoxicity Testing.
  • Jacobson-Kram D, McGovern T, (2007). Toxicological overview of impurities in pharmaceutical products. Advanced drug delivery reviews, 59(1), 38-42. DOI: 10.1016/j.addr.2006.10.007
  • Liu KT, Chen CH, (2019). Determination of Impurities in Pharmaceuticals: Why and How?. In Quality Management and Quality Control-New Trends and Developments. IntechOpen. DOI: 10.5772/intechopen.83849
  • Mike F, Pehlivan SB, Öner L, (2014). Farmasötik Ürünlerde Tasarımla Kalite Yaklaşımı. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (2), 203-230.
  • Organisation for Economic Co-operation and Development (OECD), (2015). Guidance Document on Revisions to OECD Genetic Toxicology Test Guidelines.
  • Akı-Yalçın E, (2017). Kantitatif Yapı-Etki İlişkileri Analizinde Kullanılan Fizikokimyasal Parametreler (QSAR Parametreleri). Sunu. Ankara Üniversitesi. http://www.esisresearch.org/Uploads/Documents/qsar_parametreler_2017.pdf Erişim Tarihi; 03.05.2020.
  • Pilaniya K, Chandrawanshi HK, Pilaniya U, Manchandani P, Jain P, Singh B, (2010). Recent trends in the impurity profile of pharmaceuticals. J Adv Pharm Technol Res, 2010 Jul-Sep; 1(3): 302–310. DOI: 10.4103/0110-5558.72422
  • Pindelska E, Sokal A, Kolodziejski W, (2017). Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques. Advanced drug delivery reviews, 111-146. https://doi.org/10.1016/j.addr.2017.09.014
  • Plošnik A, Vračko M, Sollner Dolenc M, (2016). Mutagenic and carcinogenic structural alerts and their mechanisms of action. Arhiv za higijenu rada i toksikologiju, 67(3), 169-182. DOI: 10.1515/aiht-2016-67-2801
  • Rägo L, Santoso B, (2008). Drug Regulation: History, Present and Future, WHO, 65-76.
  • Smith S, (2009). Chiral Toxicology: It’s the Same Thing...Only Different, Toxicological Sciences, 110(1), 4–30. DOI: 10.1093/toxsci/kfp097
  • Tian Y, Chang Y, Feng YC, Zhang DS, Hu C, (2015). Isolation, identification and characterization of related substances in furbenicillin. The Journal of Antibiotics, 68(2), 133-136. DOI: 10.1038/ja.2014.145
  • Vargesson N, (2015). Thalidomide‐induced teratogenesis: History and mechanisms, Birth Defects Res C Embryo Today, Jun; 105(2): 140–156. DOI: 10.1002/bdrc.21096
  • Wu Y, Levons J, Narang AS, Raghavan K, Rao VM, (2011). Reactive impurities in excipients: profiling, identification and mitigation of drug–excipient incompatibility. AAPS PharmSciTech, 12(4), 1248-1263. DOI: 10.1208/s12249-011-9677-z
  • Ziegelbauer HE, Aubrecht J, Kleinjans JC, Ahr HJ, (2009). “Applications of toxicogenomics to study mechanisms of genotoxicity and carcinogenicity”. Toxicol Lett. 2009, 186, 36-44. DOI: 10.1016/j.toxlet.2008.08.017
There are 44 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Surgery
Journal Section Review
Authors

Mustafa Kesmen 0000-0002-6934-0463

Tülay Bakırel 0000-0001-5805-2178

Project Number 20
Publication Date December 31, 2020
Submission Date June 22, 2020
Published in Issue Year 2020 Volume: 31 Issue: 2

Cite

APA Kesmen, M., & Bakırel, T. (2020). Veteriner Tıbbî Ürünlerde Safsızlıklar. Etlik Veteriner Mikrobiyoloji Dergisi, 31(2), 201-210. https://doi.org/10.35864/evmd.753362

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